Low-dose methotrexate may preserve a stronger antileukemic effect than that of cyclosporine after modified donor lymphocyte infusion in unmanipulated haploidentical HSCT

To compare the impacts of low-dose methotrexate (MTX) with cyclosporine (CSA) on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after haploidentical modified donor lymphocyte infusion (DLI). Fifty-five consecutive patients who had relapsed acute leukemia after haploidentical hematopoietic stem cell transplantation (HSCT) and received modified DLI were retrospectively studied. Forty-one patients received CSA and 14 received low-dose MTX after DLI to prevent DLI-associated GVHD. The incidence of acute GVHD and grade 2-4 acute GVHD in MTX group showed a trend toward being higher than in CSA group (61.0% vs. 37.3%, p=0.198 and 61.0% vs. 35.5%, p=0.155). However, no significant difference in the incidence of grade 3-4 acute GVHD between two groups (p=0.982) was observed. Moreover, compared with CSA, patients treated with MTX had lower re-relapse rate (38.1% vs. 80.8%, p=0.029), better disease-free survival (DFS) (51.9% vs. 15.6%, p=0.06), and higher absolute lymphocyte counts at 30, 45, 60, and 90d after modified DLI (p<0.05). This study suggested that after haploidentical modified DLI, low-dose MTX is at least as effective as CSA in the prevention of DLI-associated GVHD and probably allowed stronger GVL effect than CSA. This phenomenon was probably due to a direct antitumor effect and a better reconstitution of lymphocytes after modified DLI induced by low-dose MTX.